查看“FGFR1扩增”的源代码

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            <strong>[[FGFR1扩增]]</strong>（<strong>[[FGFR1Amplification]]</strong>）是指<strong>[[成纤维细胞生长因子受体1]]</strong>（[[FGFR1]]）基因座在<strong>[[染色体]]</strong>上发生的异常倍增现象，属于一种关键的<strong>[[基因拷贝数变异]]</strong>（[[CNV]]）。该变异位于染色体<strong>[[8p11.23]]</strong>区域，其结果导致[[FGFR1]]蛋白在细胞膜上的高度表达，进而通过<strong>[[配体]]</strong>依赖或非依赖的方式持续激活下游<strong>[[信号通路]]</strong>。在临床肿瘤学中，[[FGFR1扩增]]是<strong>[[肺鳞癌]]</strong>（约20%）和<strong>[[雌激素受体阳性]]</strong>（[[ER+]]）<strong>[[乳腺癌]]</strong>（约10%）的重要驱动因素，被视为极具潜力的<strong>[[治疗靶点]]</strong>。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">FGFR1扩增</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">Alteration:[[FGFR1]]Amplification · 点击展开详情</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">[[致癌驱动变异]]</div>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">涉及基因</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;"><strong>[[FGFR1]]</strong></td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[染色体位置]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">[[8p11.23]]</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[检测方法]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">[[FISH]]/[[NGS]]</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">扩增标准</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">[[拷贝数]]&ge;6</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要癌种</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[肺鳞癌]]/[[乳腺癌]]</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569;">相关配体</th>
                    <td style="padding: 10px 12px;">[[FGF2]]/[[FGF4]]</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：信号通路的持续过载</h2>
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        [[FGFR1扩增]]通过增加<strong>[[基因剂量]]</strong>改变了细胞对生长信号的响应阈值，其致癌机制可概括为以下层面：
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        <li style="margin-bottom: 12px;"><strong>受体过度表达：</strong>基因扩增导致[[FGFR1]]蛋白在细胞表面极度密集，即使在极低水平的<strong>[[成纤维细胞生长因子]]</strong>（[[FGF]]）存在下也能触发强烈的活化。</li>
        <li style="margin-bottom: 12px;"><strong>[[自发二聚化]]：</strong>当受体密度超过临界点，蛋白可在无配体的情况下发生自发二聚化及<strong>[[自身磷酸化]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>级联通路激活：</strong>激活的[[FGFR1]]持续启动<strong>[[Ras-MAPK通路]]</strong>（促进增殖）、<strong>[[PI3K-AKT通路]]</strong>（抑制凋亡）和<strong>[[STAT信号]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>[[内分泌治疗]]耐药：</strong>在乳腺癌中，[[FGFR1]]信号可作为旁路机制，代偿受抑的<strong>[[雌激素受体]]</strong>通路，导致患者对常规药物产生耐药。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床图谱：常见癌症中的FGFR1扩增分布</h2>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">癌症类型</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">[[扩增频率]]</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床特征与预后</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[肺鳞癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">约15%到22%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">常伴有长期吸烟史，是肺鳞癌中最具开发价值的[[驱动突变]]之一。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[乳腺癌]] (Luminal型)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">约10%到15%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">与[[三苯氧胺]]或[[芳香化酶抑制剂]]的原发或继发耐药密切相关。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[小细胞肺癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">约5%到7%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">代表了一类对常规[[化疗]]反应较差的亚型。</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">治疗策略：针对FGFR1扩增的干预手段</h2>
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        <li style="margin-bottom: 12px;"><strong>[[非选择性TKI]]：</strong>如<strong>[[德立替尼]]</strong>（[[Lucitanib]]）或<strong>[[多韦替尼]]</strong>，虽能抑制[[FGFR1]]，但因同时作用于[[VEGFR]]，毒副作用较大。</li>
        <li style="margin-bottom: 12px;"><strong>[[高选择性TKI]]：</strong>如<strong>[[佩米替尼]]</strong>或<strong>[[厄达替尼]]</strong>。目前多项研究正聚焦于在高水平扩增人群中验证其疗效。</li>
        <li style="margin-bottom: 12px;"><strong>[[联合方案]]：</strong>在[[乳腺癌]]中，[[FGFR1]]抑制剂联合<strong>[[内分泌治疗]]</strong>（如[[氟维司群]]）旨在克服耐药，延长[[PFS]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[副作用管理]]：</strong>重点监测<strong>[[高磷血症]]</strong>、[[皮肤]]干燥及[[指甲]]病变，这些是[[FGFR]]抑制剂的类特异性反应。</li>
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        <h3 style="color: #0f172a; font-size: 1.15em; margin-bottom: 20px; border-bottom: 2px solid #3b82f6; display: inline-block; padding-bottom: 5px;">关键相关概念</h3>
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            <div style="color: #334155;"><strong style="color: #1e40af;">[[8p11骨髓增殖性综合征]]</strong>：由于[[FGFR1]]基因易位而非单纯扩增引起的一种罕见血液肿瘤。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[FISH]]</strong>：检测[[FGFR1扩增]]的金标准技术，可精确计算[[拷贝数]]比例。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[FGF23]]</strong>：调控磷代谢的关键因子，受[[FGFR1]]信号抑制影响。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[LX-039]]</strong>：兰圣生物自研的一种针对[[FGFR]]变异的候选抑制剂。</div>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
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            [1] <strong>Weiss J, et al. (2010).</strong> <em>Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer.</em> <strong>[[ScienceTranslationalMedicine]]</strong>. 2010;2(62):62ra93.<br>
            <span style="color: #475569;">[学术点评]：该项基石研究确立了[[FGFR1扩增]]作为肺鳞癌重要亚型的地位，并证实了抑制受体可诱导肿瘤缩小。</span>
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            [2] <strong>Turner N, et al. (2010).</strong> <em>FGFR1 Amplification Drives Endocrine Resistance in Breast Cancer.</em> <strong>[[CancerResearch]]</strong>. 2010;70(5):2085-2094.<br>
            <span style="color: #475569;">[学术点评]：明确了[[FGFR1]]信号与内分泌耐药的分子关联，为乳腺癌联合靶向治疗提供了理论基础。</span>
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            [3] <strong>Kroep JR, et al. (2022).</strong> <em>FGFR inhibitors in oncology: A review of current and future strategies.</em> <strong>[[TheLancetOncology]]</strong>. 2022.<br>
            <span style="color: #475569;">[学术点评]：[Academic Review] 综合分析了目前针对[[FGFR]]扩增及其他变异的新药开发挑战。</span>
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            [[FGFR1扩增]] ([[FGFR1Amplification]]) · 知识图谱导航
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[分子生物学]]</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[拷贝数变异]] • [[RTK家族]] • [[染色体8p11]] • [[配体依赖激活]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[核心癌种]]</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[肺鳞癌]] • [[HR+乳腺癌]] • [[小细胞肺癌]] • [[头颈部肿瘤]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[靶向药物]]</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[佩米替尼]] • [[厄达替尼]] • [[德立替尼]] • [[LX-039]] • [[多韦替尼]]</td>
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